# Advances in the multifunctional roles of CX3CL1 in the central nervous system

## TL;DR

CX3CL1 is a unique brain protein that both protects and can cause inflammation, and may help treat brain diseases.

## Contribution

The study reveals CX3CL1's dual role in neuroinflammation and cognitive decline, offering new therapeutic insights.

## Key findings

- CX3CL1 restrains microglial hyperactivation but can promote inflammation under chronic stress.
- CX3CL1 preserves synaptic plasticity and supports remyelination in the CNS.
- Reduced CX3CL1 levels with age correlate with cognitive decline, which exogenous CX3CL1 can partially reverse.

## Abstract

C-X3-C motif chemokine ligand 1 (CX3CL1), a structurally unique chemokine in the central nervous system (CNS), shapes physiological and pathological processes via specific binding to its receptor, C-X3-C motif chemokine receptor 1 (CX3CR1). Empirical evidence indicates that this signaling axis exerts dual neuroinflammatory effects: It restrains microglial hyperactivation, yet can promote inflammation under conditions such as chronic stress. Notably, it preserves synaptic plasticity and facilitates remyelination. Age-associated reductions in CX3CL1 exhibit a strong correlation with cognitive decline; administration of exogenous CX3CL1 partially mitigates these deficits. This study provides a comprehensive account of the multifaceted functions and regulatory mechanisms of CX3CL1 in CNS diseases, thereby establishing a basis for potential new therapeutic targets.